Soapbox Science

Looking back: The mystery of Knut, the famous polar bear

Guest blog by Alex Greenwood, Leibniz Institute for Zoo and Wildlife Research (IZW), Germany

Knut the polar bear

Berlin Zoological Garden

Earlier in 2016 Scientific Reports celebrated its fifth anniversary. You can view our interactive infographic and blogs marking this occasion here.

As this fifth anniversary year draws to a close, we’ve got back in touch with authors from two popular papers from recent years.

Now that some time has passed, we wanted to know about their experience publishing with the journal, what impact they felt their research has had and what’s surprised them.

First up, here is an interview with Alex Greenwood, an author of the study in Scientific Reports that suggested Knut, the famous hand-reared polar bear from the Berlin Zoological Gardens, suffered from anti-NMDA receptor (NMDAR) encephalitis. The study “Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut” is available here.

We spoke to Professor Greenwood about the research.

Alex Greenwood

Could you give a brief overview of your paper in Scientific Reports?

Our study in Scientific Reports was the culmination of our efforts to determine what caused the death of Knut, the world famous polar bear. A necropsy performed at the Leibniz Institute for Zoo and Wildlife Research (IZW) determined that Knut had inflammation of the brain (encephalitis) and suggested the cause was an infectious agent. However, intensive, cutting-edge pathogen diagnostics immediately after necropsy did not identify any causal pathogen. The negative results required completely new thinking and approaches; among the candidates was an autoimmune disease.

Similar to Knut’s case, many human medical cases went undiagnosed for decades because a causative pathogen could not be linked to the symptoms of encephalitis. In 2007 it was revealed that many of these patients suffered from an autoimmune disease (where the patient’s antibodies attack their own brain as foreign material). The most common among these diseases is anti-NMDA disease — where the patient’s antibodies attack the N-methyl-D aspartate receptor in the brain, leading to severe inflammation. The team of Dr. Harald Prüß at Charité/German Center for Neurodegenerative Diseases (DZNE) Berlin, who are experts on these diseases, reasoned that this could potentially explain Knut’s case. After extensive testing, the teams at the IZW and Charité determined that this in fact is what explained Knut’s encephalitis.

What sort of impact have your findings had?

Anti-NMDA disease is now more broadly recognized among the public because of its association with Knut. This will hopefully lead to improvements in diagnosis of this and related diseases, particularly because in humans the presentation of the disease can be quite variable.  Zoo and wildlife veterinarians have realized that not all diseases, even those where a pathogen is suspected, will necessarily be the result of infectious diseases and that management practices may have to take this into consideration. For example, the counterintuitive management strategy in such an encephalitis case would be to suppress the immune system — not a therapeutic intervention one would necessarily consider in the case of a pathogen caused disease. At the very least, it is quite likely that new cases in more species will be identified, expanding this disease’s occurrence to mammals in general. Others have already seen rarer neuronal receptor diseases in domestic cats. These diseases are unlikely to be restricted to cats and polar bears.

Was there anything surprising about this research?

Upon taking on Knut’s case, the flood of expert opinions, all supporting an infectious pathogen as the cause of Knut’s symptoms, was deafening. It was interesting to see how this guided so many of the contributions from collaborators and spectators. In many ways this narrowed the number of avenues initially investigated. We tried to keep an open mind but some of the ideas we had — including an aberrant immune reaction — were beyond what we thought is amenable to study in wildlife diseases, given that so much less is known about wildlife biology than human or laboratory animal biology.  Many of the techniques we considered would have likely yielded data difficult to interpret, without the fundamental knowledge of, for example, which proteins are expressed where in a polar bear.

Their sharp eyes and the constructive collaboration with Dr. Harald Prüß and his team made it possible to consider the improbable — and demonstrate that the improbable was in fact the answer. The ability to transfer the techniques from human medicine to a polar bear case was both unusual and extremely fortunate.

Was there a particular reason you chose to publish in Scientific Reports?

The study performed, in essence, represents a case report. Scientific Reports recognized that the findings in this case go well beyond Knut as an individual and allowed it to be peer reviewed. The identification of this disorder, which before Knut was only recognized as a human disease, must now be considered a disease of mammals with consequences for diagnosis and management in veterinary medicine in particular. Because Scientific Reports is open access this means anyone who is confronted with a similar case and suspects an autoimmune disease can refer to our study and our methods with no barriers to access. This was an important element in our consideration of where to submit the manuscript.

Professor Alex D. Greenwood is the Head of the Department of Wildlife Diseases at the Leibniz Institute for Zoo and Wildlife Research (IZW) and Professor of Wildlife Diseases in the Department of Veterinary Medicine of the Freie Universität Berlin, both institutions in Berlin, Germany. His work has focused on evolutionary virology, primarily on retroviruses and more recently herpes viruses in wildlife. He integrates ancient DNA, evolutionary and ecological analyses in most of his work and also has an interest in high throughput diagnostic methods. His work with Knut the polar bear intersected with the latter interest.

On Friday (23 December) we will post a second guest blog from another Scientific Reports author. 

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